Cupressuflavone isolated from Cupressus torulosa ameliorates diabetic nephropathy by inhibiting oxidative stress and inflammation through Nrf-2/ NF-κB signalling axis

Cupressuflavone (CTM-01), a potential biflavonoid isolated from Cupressus torulosa exhibited antimicrobial, analgesic, cytotoxic and wound-healing properties. The present study aims to evaluate the renoprotective effects through in vitro and in vivo models as well as elucidate the underlying mechanisms of its nephroprotective action under diabetic conditions. The in vitro effects of CTM-01 on cell viability (25, 50, and 100 µM) and intracellular ROS production were evaluated in cultured normal rat proximal epithelial cells (NRK-52E) grown under high glucose conditions (30 mM) while streptozotocin (STZ) induced rats were treated with CTM-01 at 25 mg/kg for four weeks and the effects on different biochemical, histological, and molecular parameters were studied. The oral administration of CTM-01 (25 mg/kg) in diabetic rats restored the fasting blood glucose to normal control levels, and markedly ameliorated renal dysfunction as evidenced by a significant decrease in serum creatinine, urea, and albumin. Additionally, CTM-01-treated rats exhibited a significant increase in the levels of renal antioxidants such as SOD, CAT, and GSH as well as decreased MDA content against diabetic control rats and restored kidney damage in CTM-01-treated diabetic rats. Moreover, CTM-01 significantly increased the level of NRF-2 and downregulated the expression of p-NF-κB. This novel study provides strong evidence to support the potent anti-oxidative and renoprotective properties of CTM-01 in alleviating oxidative damage and inflammation through the suppression of the Nrf-2/NF-κB signalling axis for the effective management of diabetic nephropathy.